Practical Syntheses of Chiral -Amino Acids and Chiral Half-Esters by Kinetic Resolution of Urethane-Protected 
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- 作者：Yutaka Ishii ; Ryosuke Fujimoto ; Masafumi Mikami ; Satoshi Murakami ; Yasushi Miki ; Yoshiro Furukawa
- 刊名：Organic Process Research & Development
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：11
- 期：3
- 页码：609 - 615
- 全文大小：114K
- 年卷期：v.11,no.3(May 2007)
- ISSN：1520-586X
文摘
The large-scale applications of the kinetic resolution of urethane-protected 
-amino acid N-carboxyanhydrides (UNCAs) and thedesymmetrization of cyclic meso-anhydrides using modifiedcinchona alkaloids are described. These asymmetric reactionsare effective organocatalytic methods for the synthesis of chiral-amino acids 6 and chiral half-esters 2 on an industrial scale,because the organocatalyst recovery and product purificationcan be carried out by a simple extractive procedure obviatinga chromatographic purification step. The modified cinchonaalkaloid catalysts (DHQD)2AQN and (DHQ)2AQN, as reportedby Deng and co-workers, are not readily available and thereforenot suitable for industrial-scale synthesis. Various O-alkylatedquinidine and quinine derivatives were prepared and screenedas catalysts for the kinetic resolution of phenylalanine UNCAwith alcohol. The readily prepared O-propargylquinidine(OPQD) and O-propargylquinine (OPQ) were discovered to behighly enantioselective and practical catalysts. These newcatalysts were applied to the synthesis of chiral propargylglycine24 and the key intermediate of BAY10-8888/PLD-118, 26, onan industrial scale, by the kinetic resolution of UNCA 22 andthe desymmetrization of cyclic meso-anhydride 25, respectively.
-amino acid N-carboxyanhydrides (UNCAs) and thedesymmetrization of cyclic meso-anhydrides using modifiedcinchona alkaloids are described. These asymmetric reactionsare effective organocatalytic methods for the synthesis of chiral-amino acids 6 and chiral half-esters 2 on an industrial scale,because the organocatalyst recovery and product purificationcan be carried out by a simple extractive procedure obviatinga chromatographic purification step. The modified cinchonaalkaloid catalysts (DHQD)2AQN and (DHQ)2AQN, as reportedby Deng and co-workers, are not readily available and thereforenot suitable for industrial-scale synthesis. Various O-alkylatedquinidine and quinine derivatives were prepared and screenedas catalysts for the kinetic resolution of phenylalanine UNCAwith alcohol. The readily prepared O-propargylquinidine(OPQD) and O-propargylquinine (OPQ) were discovered to behighly enantioselective and practical catalysts. These newcatalysts were applied to the synthesis of chiral propargylglycine24 and the key intermediate of BAY10-8888/PLD-118, 26, onan industrial scale, by the kinetic resolution of UNCA 22 andthe desymmetrization of cyclic meso-anhydride 25, respectively.